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立体定向消融放疗用于肾细胞癌颅外转移的安全性和有效性

Safety and Efficacy of Stereotactic Ablative Radiation Therapy for Renal Cell Carcinoma Extracranial Metastases.

作者信息

Wang Chiachien Jake, Christie Alana, Lin Mu-Han, Jung Matthew, Weix Derek, Huelsmann Lorel, Kuhn Kristin, Meyer Jeffrey, Desai Neil, Kim D W Nathan, Pedrosa Ivan, Margulis Vitaly, Cadeddu Jeffrey, Sagalowsky Arthur, Gahan Jeffrey, Laine Aaron, Xie Xian-Jin, Choy Hak, Brugarolas James, Timmerman Robert, Hannan Raquibul

机构信息

Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.

Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas.

出版信息

Int J Radiat Oncol Biol Phys. 2017 May 1;98(1):91-100. doi: 10.1016/j.ijrobp.2017.01.032.

Abstract

PURPOSE

Renal cell carcinoma is refractory to conventional radiation therapy but responds to higher doses per fraction. However, the dosimetric data and clinical factors affecting local control (LC) are largely unknown. We aimed to evaluate the safety and efficacy of stereotactic ablative radiation therapy (SAbR) for extracranial renal cell carcinoma metastases.

METHODS AND MATERIALS

We reviewed 175 metastatic lesions from 84 patients treated with SAbR between 2005 and 2015. LC and toxicity after SAbR were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Predictors of local failure were analyzed with χ, Kaplan-Meier, and log-rank tests.

RESULTS

In most cases (74%), SAbR was delivered with total doses of 40 to 60 Gy, 30 to 54 Gy, and 20 to 40 Gy in 5 fractions, 3 fractions, and a single fraction, respectively. The median biologically effective dose (BED) using the universal survival model was 134.5 Gy. The 1-year LC rate after SAbR was 91.2% (95% confidence interval, 84.9%-95.0%; median follow-up, 16.7 months). Local failures were associated with prior radiation therapy (hazard ratio [HR], 10.49; P<.0001), palliative-intent radiation therapy (HR, 4.63; P=.0189), spinal location (HR, 5.36; P=.0041), previous systemic therapy status (0-1 vs >1; HR, 3.52; P=.0217), and BED <115 Gy (HR, 3.45; P=.0254). Dose received by 99% of the target volume was the strongest dosimetric predictor for LC. Upon multivariate analysis, dose received by 99% of the target volume greater than BED of 98.7 Gy and systemic therapy status remained significant (HR, 0.12 and 3.64, with P=.0014 and P=.0472, respectively). Acute and late grade 3 toxicities attributed to SAbR were observed in 3 patients (1.7%) and 5 patients (2.9%), respectively.

CONCLUSIONS

SAbR demonstrated excellent LC of metastatic renal cell carcinoma with a favorable safety profile when an adequate dose and coverage were applied. Multimodality treatment with surgery should be considered for reirradiation or vertebral metastasis. A higher radiation dose may be required in patients who received previous systemic therapies.

摘要

目的

肾细胞癌对传统放射治疗具有抗性,但对较高的分次剂量有反应。然而,影响局部控制(LC)的剂量学数据和临床因素在很大程度上尚不清楚。我们旨在评估立体定向消融放射治疗(SAbR)用于颅外肾细胞癌转移灶的安全性和有效性。

方法和材料

我们回顾了2005年至2015年间接受SAbR治疗的84例患者的175个转移病灶。采用实体瘤疗效评价标准(RECIST)1.1版和不良事件通用术语标准(CTCAE)4.0版评估SAbR后的局部控制和毒性。使用χ检验、Kaplan-Meier法和对数秩检验分析局部失败的预测因素。

结果

在大多数情况下(74%),SAbR分别以40至60 Gy、30至54 Gy和20至40 Gy的总剂量分5次、3次和单次给予。使用通用生存模型计算的中位生物等效剂量(BED)为134.5 Gy。SAbR后的1年局部控制率为91.2%(95%置信区间,84.9%-95.0%;中位随访时间,16.7个月)。局部失败与既往放疗(风险比[HR],10.49;P<0.0001)、姑息性放疗(HR,4.63;P=0.0189)、脊柱部位(HR,5.36;P=0.0041)、既往全身治疗状态(0-1次与>1次;HR,3.52;P=0.0217)以及BED<115 Gy(HR,3.45;P=0.0254)相关。99%靶体积接受的剂量是局部控制最强的剂量学预测因素。多因素分析显示,99%靶体积接受的剂量大于98.7 Gy的BED以及全身治疗状态仍然具有显著性(HR分别为0.12和3.64,P分别为0.0014和0.0472)。分别有3例患者(1.7%)和5例患者(2.9%)观察到SAbR所致的急性3级和晚期3级毒性反应。

结论

当给予足够的剂量和靶区覆盖时,SAbR显示出对转移性肾细胞癌优异的局部控制效果以及良好的安全性。对于再次放疗或椎体转移,应考虑手术的多模式治疗。既往接受过全身治疗的患者可能需要更高的放射剂量。

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